Polarizability matters in enantio-selection.

The prevalence of chirality, or, handedness in biological world is a fundamental phenomenon and a characteristic hallmark of life. Thus, understanding the origin of enantio-selection, i.e., the sense and magnitude of asymmetric induction, has been a long-pursued goal in asymmetric catalysis. Herein, we demonstrated a polarizability-derived electronic effect that was shown to be capable of rationalizing a broad range of stereochemical observations made in the field of asymmetric catalysis. This effect provided a consistent enantio-control model for the prediction of major enantiomers formed in a ruthenium-catalyzed asymmetric transfer hydrogenations of ketones. Direct and quantitative linear free energy relationships between substrates' local polarizabilities and observed enantio-selectivity were also revealed in three widely known asymmetric catalytic systems covering both reductions and oxidations. This broadly applicable polarizability-based electronic effect, in conjunction with conventional wisdom mainly leveraging on steric effect considerations, should aid rational design of enantio-selective processes for better production of chiral substances.

Triethyl amine as an effective reducing agent for sulfoxide deoxygenation.

Enabled by triethyl amine (Et3N) and thionyl chloride (SOCl2), an efficient and practical protocol for deoxygenation of sulfoxide to sulfide was developed. This new method features a wide range of substrate scope, including diaryl, dialkyl and aryl alkyl substituted sulfoxides. Detailed mechanistic investigations reveal the crucial role played by Et3N as an electron-donating reductant rather than a hydrogen-atom donor.

Fully Integrated Microfluidic Platform for Multiplexed Detection of Hunov by a Dynamic Confined-Space-Implemented One-Pot Rpa-Lamp System.

Human norovirus (HuNoV) is the leading cause of nonbacterial acute gastroenteritis, which is highly infectious, rapidly evolving, and easily transmitted through feces. The accurate and early detection of HuNoV subtypes is essential for effective treatment, early surveillance, risk assessment, and disease prevention. In this study, a portable multiplex HuNoV detection platform that combines integrated microfluidics and cascade isothermal amplification, using a streamlined protocol for clinical fecal-based diagnosis is presented. To overcome the problems of carryover contamination and the incompatibility between recombinase polymerase amplification (RPA) and loop-mediated isothermal amplification (LAMP), a Dynamic confined-space-implemented One-pot RPA-LAMP colorimetric detection system (DORLA) is developed by creating a hydrogen bond network. The DORLA system exhibits excellent sensitivity, with detection limits of 10 copies µL-1 and 1 copy µL-1 for HuNoV GI and GII, respectively. In addition, a portable diagnostic platform consisting of a thermostatic control module and an integrated 3D-printed microfluidic chip for specific HuNoV capture, nucleic acid pretreatment, and DORLA detection, which enables simultaneous diagnosis of HuNoV GI and GII is developed. A DORLA-based microfluidic platform exhibits satisfactory performance with high sensitivity and portability, and has high potential for the rapid point-of-care detection of HuNoV in clinical fecal samples, particularly in resource-limited settings.

Alternations of antibiotic resistance genes and microbial community dynamics on shared bicycles before and after pandemic lockdown.

The prevalence of shared bicycles has raised concerns over their potential to transmit pathogens and microbes harboring antibiotic resistance genes (ARGs), which pose significant human health risks. This study investigated the impact of anthropogenic activities on the composition of ARGs and microbial communities on shared bicycles during the COVID-19 pandemic and subsequent lockdown when shared bicycle usage was altered. A total of 600 swab samples from shared bicycle surfaces were collected in Shanghai before and during COVID-19 lockdown periods. Even during lockdown, 12 out of 14 initially detected ARG subtypes persisted, indicating their tenacity in the face of reduced anthropogenic activities. These ARGs displayed significantly higher absolute and relative abundance levels before the lockdown. In addition, the percentage of potential pathogens in the total microbial abundance remained at 0.029 % during the lockdown, which was lower than the pre-lockdown percentage of 0.035 % and suggested that these risks persist within shared bicycle systems. Interestingly, although microbial abundance decreased without the consecutive use of shared bicycles during lockdown, the microbial diversity increased under the impact of restricted anthropogenic activities (p < 0.001). This emphasizes the need for continuous monitoring and research to comprehend microbial community behaviors in various environments. This study uncovered the underlying impacts of the COVID-19 lockdown on the microbial and ARG communities of shared bicycles, providing comprehensive insights into the health management of shared transportation. Although lockdown can decrease the abundance of ARGs and potential pathogens, additional interventions are needed to prevent their continued spread.

Understanding the China-Tanzania Malaria Control Project: lessons learned from a multi-stakeholder qualitative study.

Background: Tanzania is among the countries with the highest malaria cases and deaths worldwide, where vulnerable populations have been severely affected due to poverty and weakness in health system and infrastructure. The China-Tanzania Malaria Control Project (the Project) was a two-phase global health intervention project implemented between 2015 and 2021 that aimed to transfer project-designated intervention experience in malaria elimination to the Tanzanian health system. This study aims to identify the barriers and facilitators encountered during the Project and to improve our understanding of the emerging phenomenon of South-South global health collaboration. Methods: We conducted thematic analysis of qualitative data collected from a purposive sample of 14 participants from multiple stakeholders including project management office, project implementation agency, funding partners and external evaluators of the Project. A conceptual framework was developed to construct the interviews guides. The interviews were transcribed verbatim, crossover checked, translated into English, and analyzed with NVivo 12.0. We conducted the open coding followed by the axial coding based on the Grounded Theory to generate themes and subthemes, and identified key influencing factors that aided or hindered the malaria control in Tanzania. Results: The findings suggested that malaria control strategies should largely be tailored due to varied socioeconomic contexts. The perceived enablers in practice include project-designated intervention experiences and technologies, professional and self-learning capabilities of the implementation team, sustainable financial assistance, and support from the international partners. The barriers include the shortage of global health talents, existing gaps to meet international standards, defects in internal communication mechanisms, inadequacy of intergovernmental dialogue, and limitations in logistical arrangements. A checklist and policy implications for China's future engagement in malaria control in resource-limited settings have been proposed. Conclusions: The initiative of Health Silk Road has generated strong global interest in promoting development assistance in health. In the hope of generalizing the evidence-based interventions to high malaria-endemic countries in Africa, the need for China to carefully face the challenges of funding gaps and the lack of support from recipient governments remains ongoing. It is recommended that China should form an institutionalized scheme and sustainable funding pool to ensure the steady progress of development assistance in health.

Assessing food security performance from the One Health concept: an evaluation tool based on the Global One Health Index.

BACKGROUND: Food systems instantiate the complex interdependencies across humans, physical environments, and other organisms. Applying One Health approaches for agri-food system transformation, which adopts integrated and unifying approaches to optimize the overall health of humans, animals, plants, and environments, is crucial to enhance the sustainability of food systems. This study develops a potential assessment tool, named the global One Health index-Food Security (GOHI-FS), aiming to evaluate food security performance across countries/territories from One Health perspective and identify relevant gaps that need to be improved for sustainable food systems. METHODS: We comprehensively reviewed existing frameworks and elements of food security. The indicator framework of GOHI-FS was conceptualized following the structure-process-outcome model and confirmed by expert advisory. Publicly available data in 2020 was collected for each indicator. The weighting strategy was determined by the Fuzzy Analytical Hierarchy Process. The data for each indicator was normalized and aggregated by weighted arithmetic mean. Linear regressions were performed to evaluate the associations of GOHI-FS with health and social-economic indicators. RESULTS: The GOHI-FS includes 5 first-level indicators, 19 second-level indicators and 45 third-level indicators. There were 146 countries/territories enrolled for evaluation. The highest average score of first-level indicators was Nutrition (69.8) and the lowest was Government Support and Response (31.3). There was regional heterogeneity of GOHI-FS scores. Higher median scores with interquartile range (IQR) were shown in North America (median: 76.1, IQR: 75.5-76.7), followed by Europe and Central Asia (median: 66.9, IQR: 60.1-74.3), East Asia and the Pacific (median: 60.6, IQR: 55.5-68.7), Latin America and the Caribbean (median: 60.2, IQR: 57.8-65.0), Middle East and North Africa (median: 56.6, IQR: 52.0-62.8), South Asia (median: 51.1, IQR: 46.7-53.8), and sub-Saharan Africa (median: 41.4, IQR: 37.2-46.5). We also found significant associations between GOHI-FS and GDP per capita, socio-demographic index, health expenditure and life expectancy. CONCLUSIONS: GOHI-FS is a potential assessment tool to understand the gaps in food security across countries/territories under the One Health concept. The pilot findings suggest notable gaps for sub-Saharan Africa in numerous aspects. Broad actions are needed globally to promote government support and response for food security.

Multiplex Detection of Infectious Diseases on Microfluidic Platforms.

Infectious diseases contribute significantly to the global disease burden. Sensitive and accurate screening methods are some of the most effective means of identifying sources of infection and controlling infectivity. Conventional detecting strategies such as quantitative polymerase chain reaction (qPCR), DNA sequencing, and mass spectrometry typically require bulky equipment and well-trained personnel. Therefore, mass screening of a large population using conventional strategies during pandemic periods often requires additional manpower, resources, and time, which cannot be guaranteed in resource-limited settings. Recently, emerging microfluidic technologies have shown the potential to replace conventional methods in performing point-of-care detection because they are automated, miniaturized, and integrated. By exploiting the spatial separation of detection sites, microfluidic platforms can enable the multiplex detection of infectious diseases to reduce the possibility of misdiagnosis and incomplete diagnosis of infectious diseases with similar symptoms. This review presents the recent advances in microfluidic platforms used for multiplex detection of infectious diseases, including microfluidic immunosensors and microfluidic nucleic acid sensors. As representative microfluidic platforms, lateral flow immunoassay (LFIA) platforms, polymer-based chips, paper-based devices, and droplet-based devices will be discussed in detail. In addition, the current challenges, commercialization, and prospects are proposed to promote the application of microfluidic platforms in infectious disease detection.

Amplification-free CRISPR/Cas detection technology: challenges, strategies, and perspectives.

Rapid and accurate molecular diagnosis is a prerequisite for precision medicine, food safety, and environmental monitoring. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas)-based detection, as a cutting-edged technique, has become an immensely effective tool for molecular diagnosis because of its outstanding advantages including attomolar level sensitivity, sequence-targeted single-base specificity, and rapid turnover time. However, the CRISPR/Cas-based detection methods typically require a pre-amplification step to elevate the concentration of the analyte, which may produce non-specific amplicons, prolong the detection time, and raise the risk of carryover contamination. Hence, various strategies for target amplification-free CRISPR/Cas-based detection have been developed, aiming to minimize the sensitivity loss due to lack of pre-amplification, enable detection for non-nucleic acid targets, and facilitate integration in portable devices. In this review, the current status and challenges of target amplification-free CRISPR/Cas-based detection are first summarized, followed by highlighting the four main strategies to promote the performance of target amplification-free CRISPR/Cas-based technology. Furthermore, we discuss future perspectives that will contribute to developing more efficient amplification-free CRISPR/Cas detection systems.

Asymmetric Dihydroxylation-Based Kinetic Resolution of Allylic Amides Enabled by Noncovalent π-Interactions.

While Sharpless asymmetric dihydroxylation is widely utilized to convert various alkenes into diols with excellent enantioselectivies, kinetic resolution by means of this fundamental catalysis has generally proven to be ineffective. Here we report that, by relying on noncovalent π-interactions that purposely include the substrate's stereocenter in the corresponding catalyst-substrate interaction framework, AD-based kinetic resolution of allylic amides is realized. This method enables such versatile chiral building blocks to be easily accessed with excellent enantiomeric excesses (ee's).

Clustered Regularly Interspaced short palindromic repeats-Based Microfluidic System in Infectious Diseases Diagnosis: Current Status, Challenges, and Perspectives.

Mitigating the spread of global infectious diseases requires rapid and accurate diagnostic tools. Conventional diagnostic techniques for infectious diseases typically require sophisticated equipment and are time consuming. Emerging clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) detection systems have shown remarkable potential as next-generation diagnostic tools to achieve rapid, sensitive, specific, and field-deployable diagnoses of infectious diseases, based on state-of-the-art microfluidic platforms. Therefore, a review of recent advances in CRISPR-based microfluidic systems for infectious diseases diagnosis is urgently required. This review highlights the mechanisms of CRISPR/Cas biosensing and cutting-edge microfluidic devices including paper, digital, and integrated wearable platforms. Strategies to simplify sample pretreatment, improve diagnostic performance, and achieve integrated detection are discussed. Current challenges and future perspectives contributing to the development of more effective CRISPR-based microfluidic diagnostic systems are also proposed.

Towards a global One Health index: a potential assessment tool for One Health performance.

BACKGROUND: A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed. METHODS: We describe five steps towards a global One Health index (GOHI), including (i) framework formulation; (ii) indicator selection; (iii) database building; (iv) weight determination; and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators. RESULTS: The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8-65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible. CONCLUSIONS: GOHI-subject to rigorous validation-would represent the world's first evaluation tool that constructs the conceptual framework from a holistic perspective of One Health. Future application of GOHI might promote a common understanding of a strong One Health approach and provide reference for promoting effective measures to strengthen One Health capacity building. With further adaptations under various scenarios, GOHI, along with its technical protocols and databases, will be updated regularly to address current technical limitations, and capture new knowledge.

Asymmetric Synthesis of γ-Secondary Amino Alcohols via a Borrowing-Hydrogen Cascade.

The borrowing-hydrogen (or hydrogen autotransfer) process, where the catalyst dehydrogenates a substrate and formally transfers the H atom to an unsaturated intermediate, is an atom-efficient and environmentally benign transformation. Described here is an example of an asymmetric borrowing-hydrogen cascade for the formal anti-Markovnikov hydroamination of allyl alcohols to synthesize optically enriched γ-secondary amino alcohols. By exploiting the Ru-(S)-iPrPyme catalyst with minimal stereogenicity, a cascade process including dehydrogenation, conjugate addition, and asymmetric reduction was developed. The mild conditions, functional group tolerance, and broad substrate scope (54 examples) demonstrate the synthetic practicality of the catalytic system.

Efficient and Precise Micro-Injection Molding of Micro-Structured Polymer Parts Using Micro-Machined Mold Core by WEDM.

In this paper, micro-structured polymer parts were efficiently and accurately fabricated by micro-injection molding using a micro-structured mold core machined by wire electrical discharge machining (WEDM). The objective was to realize low-cost mass production and manufacturing of micro-structured polymer products. The regular micro-structured mold core was manufactured by precise WEDM. The micro-structured polymer workpieces were rapidly fabricated by micro-injection molding and the effects of the micro-injection molding process parameters on replication rate and surface roughness of micro-structured polymers were systematically investigated and analyzed. It is shown that the micro-structured polymer can be rapidly and precisely fabricated by the proposed method. The experimental results show the minimum size machining error of the micro-structured mold core and the maximum replication rate of micro-formed polymer were 0.394% and 99.12%, respectively. Meanwhile, the optimal micro-injection molding parameters, namely, jet temperature, melt temperature, injection velocity, holding pressure and holding time were 195 °C, 210 °C, 40 mm/min, 7 Mpa and 5 s, respectively. The surface roughness Ra at the groove bottom and top of the micro-structured polymer workpieces achieved minimum values of 0.805 µm and 0.972 µm, respectively.

Fabrication of Micro-Structured Polymer by Micro Injection Molding Based on Precise Micro-Ground Mold Core.

Precise micro-grinding machining was proposed to fabricate regular and controllable micro-grooved array structures on the surface of mold cores to realize the mass production and manufacturing of micro-structured polymer components by micro injection molding in this paper. First, the 3D topographies and section profiles of micro-ground mold cores and micro-formed polymers with different micro-structure parameters were presented. Then, the surface roughness of mold cores and polymers were compared. Next, the relationships between machining accuracy of mold core ground by micro-grinding and filling rates of micro-structured polymer formed by micro injection molding were investigated. Finally, the influences of micro injection molding parameters on the filling rate of micro-structures polymer were investigated. It is shown that the micro-structured polymer can be effectively and rapidly fabricated using the proposed method. The experimental results indicate the highest form accuracy of the micro-grooved mold core and the filling rate of micro-structured polymer can reach to 4.05 µm and 99.30%, respectively. It is found that the filling rate of the micro-structured polymer roughly increased with increasing machining accuracy of the mold core. The injection pressure had the greatest influence on the filling rate of the injection formed polymer, while the melt temperature had the least influence.

The tumor suppressor role of miR-155-5p in gastric cancer.

Gastric cancer (GC) is the fifth most common type of malignant tumor worldwide and the most common cause of cancer-associated mortality in China. Recent studies revealed that microRNAs (miRNAs) function in the pathogenesis of GC, and that miR-155-5p expression is downregulated in GC tissues. However, the function of miR-155-5p has not been fully identified. In the present study, it was demonstrated that overexpression of miR-155-5p inhibited GC-cell proliferation and promoted apoptosis, while downregulation of miR-155-5p promoted GC-cell proliferation and decreased the cisplatin sensitivity of GC cells. Mitogen-activated protein kinase kinase kinase 10 was demonstrated to be a potential target gene of miR-155-5p. In conclusion, an antitumor role of miR-155-5p in gastric cancer was suggested.

Camphyl-based α-diimine palladium complexes: highly efficient precatalysts for direct arylation of thiazoles in open-air.

Based on the strategy of the development of phosphine-free palladium-catalyzed direct C-H arylation, a series of camphyl-based α-diimine palladium complexes bearing sterically bulky substituents were synthesized and characterized. The palladium complexes were applied for the cross-coupling of thiazole derivatives with aryl bromides. The effect of the sterically bulky substituent on the N-aryl moiety as well as the reaction conditions was screened. Under the optimal protocols, a wide range of aryl bromides can be smoothly coupled with thiazoles in good to excellent yields in the presence of a low palladium loading of 0.2 mol% under open-air conditions.

Risk factors of urinary frequency among women aged 60 and older in Taiwan.

OBJECTIVE: To assess the associated risk factors for daytime urinary frequency among Taiwanese women aged = 60 years. MATERIALS AND METHODS: Daytime urinary frequency, defined by the International Continence Society, and its associated problems were evaluated, and medical history and sociodemographic variables were recorded. A total of 2,410 women were selected by a multistage random sampling method. The factors were assessed by frequency and Pearson's ?2 test using a significance level of < 0.05. RESULTS: A total of 621 women of those initially selected in the study died before completion of this study. Face-to-face interviews with 1,521 women were completed, producing a response rate of 85.0% (1,521/1,789 women). The prevalence of daytime urinary frequency was significantly related to body mass index (p = 0.018), diabetes mellitus (p = 0.017), hypertension (p = 0.015), previous drug allergy (p = 0.003), smoking (p = 0.005), hormone therapy (p = 0.019), parity (p = 0.019), and urinary incontinence (p = 0.000). However, there was no association between urinary frequency and previous gynecologic surgery, hysterectomy, alcohol consumption, marital status, childbirth, and age of menopause. CONCLUSION: The results of this study showed a relatively high risk of urinary frequency development in patients with urinary incontinence, diabetes mellitus, hypertension, obesity, and smoking that are preventable, modifiable, or controllable. Better quality of health education for these women, drawing their attention to the associated factors, may have an impact on the prevalence of urinary frequency.

Prevalence of urinary frequency among women aged 60 years and older in Taiwan.

OBJECTIVE: To evaluate the prevalence of daytime urinary frequency among Taiwanese women aged 60 years and older. MATERIALS AND METHODS: There were an estimated 1.25 million female residents aged 60 years and over in Taiwan in 2000. A sample of 2,410 women was selected using a multistage random sampling method. Face-to-face visits with 1,523 women were completed by trained professional interviewers within 3 months of the subjects selection. Questions about urinary frequency and other lower urinary tract symptoms, sociodemographics, reproduction, and medical and surgical histories were recorded. The factors were assessed by frequency and Pearson's Chi-squared test using a significance level of < 0.05. RESULTS: The prevalence of urinary frequency in Taiwanese women aged 60 years and over was 18.8% (286/1,521). The response rate was 85.0% (1,521/1,789). For those who complained of frequency, 45.8% voided 8-15 times a day, 37.8% voided 16-23 times a day, 1.7% voided 24-31 times and a day, and 14.7% voided more than 31 times a day. The prevalence of urinary frequency was significantly associated with age (p < 0.001). CONCLUSION: Urinary frequency is a common symptom in menopausal women and is significantly related to age. More than half of the women interviewed experienced intervals of < 1 hour between visits to the restroom during the day.

High-dose misoprostol as an alternative therapy after failed medical abortion.

OBJECTIVE: The aim of this study was to determine the complete abortion rate for the vaginal administration of high-dose misoprostol after a failed medical abortion. MATERIALS AND METHODS: When their medical abortions failed after the conventional oral administration of mifepristone and misoprostol, participants then received 1,000 microg of misoprostol vaginally. The efficacy and side effects of this treatment were evaluated. RESULTS: Twenty-seven women who failed to abort after the conventional administration of mifepristone and misoprostol were enrolled in this trial. Fourteen days after the vaginal administration of 1,000 microg misoprostol, the overall complete expulsion rate had reached 88.8% (24/27). Most adverse effects were mild to moderate and did not require treatment. CONCLUSION: The vaginal administration of 1,000 microg misoprostol as a salvage therapy after a failed medical abortion appears to be a safe and highly effective alternative to surgical intervention.